How could a hormone aid weight loss in obesity?

Research in humans and monkeys suggests that lipocalin-2 (LCN2), a hormone that plays a role in feeling full after eating a meal, may help with weight loss.
Previous studies have shown that mice given LCN2 for a period of time reduce their appetite and body weight, improve their sugar metabolism, and increase energy expenditure.
A new paper appearing in eLife magazine suggests that the hormone has similar effects in primates such as monkeys and humans. This may mean that LCN2 can help people with obesity lose weight.
Obesity is an increasingly serious health problem worldwide. According to the World Health Organization (WHO), at least 2.8 million people die each year as a result of being obese or overweight.
This condition is also linked to other chronic health problems, such as: B. Type 2 diabetes, coronary artery disease, stroke, cancer and depression.
Doctors usually classify people as obese when they have a body mass index (BMI) of 25 or greater, and they tend to classify people as obese when they have a BMI of 30 or greater.
It is currently difficult to reduce obesity because of the limited understanding of the body's mechanisms by which to maintain a balance between weight, energy intake, and energy expenditure.
For example, when people who have been obese for a long time lose weight, their body slows down their metabolism, which can ultimately lead to weight gain.
In general, diet and exercise programs for weight loss tend to be short-term, while known pharmacological therapies raise safety concerns and have limited effectiveness.
The lead study author Dr. Peristera-Ioanna Petropoulou and colleagues believe that further research on LCN2 may lead to a new way of reducing obesity.
During the study, Dr. Petropoulou is a postdoctoral fellow at Columbia University's Irving Medical Center in New York City, NY. She is now a member of the Helmholtz Diabetes Center in the Helmholtz Center Munich in Germany.
“LCN2 acts as a signal for feeling full after a meal and causes mice to limit their food intake. It does this by acting on the hypothalamus in the brain. We wanted to find out whether LCN2 has similar effects in humans and whether a dose of it can cross the blood-brain barrier. "
- Dr. Peristera-Ioanna Petropoulou

 How does LCN2 work?

LCN2 is a hormone that is produced in the bone cells of mammals, including humans.
The study's authors analyzed data from four previous studies that included people of "normal weight", people who were overweight, people who were obese, and people who were severely obese. These showed that the concentration of LCN2 in the blood of people of normal weight increased after eating.
It peaks around 45 to 60 minutes after eating, and during the same period, people's hunger tends to decrease.
Some overweight people had smaller initial increases in LCN2 levels, followed by a decrease, and their feeling of fullness after eating a meal was reduced.
The LCN2 levels of people with obesity decreased after eating. As a result, researchers believe that regulating LCN2 may be key to understanding, and possibly reducing, obesity.

LCN2 in mice and monkeys

 Previous research has shown that injection of LCN2 into lean mice and those with obesity decreased their appetite by activating receptors in the hypothalamus. This is a part of the brain that is responsible for feeling hungry and full.
Researchers have identified mutations in the receptors that LCN2 works on as a common cause of obesity.
LCN2 works in mice by crossing the blood-brain barrier. This is a barrier created by the unique properties of the smallest blood vessels in the central nervous system. Its job is to regulate which molecules can get into the brain from the bloodstream.
It ensures that the brain receives the molecules it needs to function, and it also acts as a barrier that protects the brain from pollutants.
The new study suggests that LCN2 is able to cross the blood-brain barrier and bind to the hypothalamus in monkeys. This can mean that it works the same way in humans.
"We have shown that LCN2 reaches the brain, reaches the hypothalamus and suppresses food intake in non-human primates," says lead study author Prof. Stavroula Kousteni.
The study also suggests that like mice, monkeys' appetites decrease when given LCN2.
In the study, one group of monkeys received LCN2 and another group received saline for one week. The food consumption of the monkeys treated with LCN2 decreased by 27%, while it decreased by 25% in the monkeys that received the saline solution.
The researchers also observed weight loss over a short period of time. However, other observed metabolic parameters did not change significantly.
However, due to the small number of monkeys involved in the study, more research is needed to definitively prove the results.
 Is it safe?
An important question of the study was whether or not the administration of LCN2 to primates had dangerous side effects.
Researchers regularly collected and analyzed blood samples from monkeys and looked for the usual indicators of liver and kidney damage or toxicity. However, they did not find any significant changes in these markers.
This suggests that LCN2 is a surefire way to reduce feelings of hunger. As a result, it can have the potential to become a new method for achieving and maintaining weight loss.
The study's authors believe that more, more extensive research is needed on how BMI, food composition, and other factors affect the response to LCN2 in humans.
However, these initial results suggest that scientists in the future may develop an LCN2-based intervention to safely reduce overweight and obesity.
"Our results show that the hormone can curb appetite with negligible toxicity and lay the foundation for the next stage of LCN2 tests for clinical use," concludes Prof. Kousteni